We have studied the expression of TIMP-1 in lymphoid tissue. TIMP-1 is not expressed by isolated peripheral blood B-cells or tonsillar B- cells, even after stimulation with a panel of cytokines. TIMP-1 is also not expressed by low grade B-cell lymphoma cell lines. TIMP-1 is, however, expressed by four out of eight Burkitt cell lines studied. In vitro studies indicate that the cell lines expressing TIMP-1 have a higher invasion potential. In the nude mouse, TIMP-1 expressing cell lines are more tumorigenic and invasive. The TIMP-1 negative cell lines are not invasive and have a low incidence of tumor formation. The TIMP-1 expressing cell lines are resistant to cold shock induced apoptosis while the TIMP-1 negative cell lines readily undergo apoptosis. We have infected TIMP-1 negative cell lines with a retroviral construct containing TIMP-1 and have isolated TIMP-1 expressing clones. TIMP-1 expression appears to have increased the growth rate compared to retrovirus alone. We are currently studying the effect of TIMP-1 on invasiveness and apoptosis.